Genetic Variant ORM1:p.Arg38Leu (chr9-114323246-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000607.4(ORM1):c.113G>T(p.Arg38Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R38Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 24)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ORM1
NM_000607.4 missense, splice_region

Scores

Splicing: ADA: 0.00007516

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.41

Publications

26 publications found

Variant links:

Genes affected

ORM1 (HGNC:8498): (orosomucoid 1) This gene encodes a key acute phase plasma protein. Because of its increase due to acute inflammation, this protein is classified as an acute-phase reactant. The specific function of this protein has not yet been determined; however, it may be involved in aspects of immunosuppression. [provided by RefSeq, Jul 2008]

ORM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11764759).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000607.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORM1	NM_000607.4	MANE Select	c.113G>T	p.Arg38Leu	missense splice_region	Exon 1 of 6	NP_000598.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORM1	ENST00000259396.9	TSL:1 MANE Select	c.113G>T	p.Arg38Leu	missense splice_region	Exon 1 of 6	ENSP00000259396.8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

142568

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.03e-7

AC:

AN:

1421724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705940

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31752

American (AMR)

AF:

0.00

AC:

AN:

40454

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25482

East Asian (EAS)

AF:

0.0000267

AC:

AN:

37474

South Asian (SAS)

AF:

0.00

AC:

AN:

82578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088406

Other (OTH)

AF:

0.00

AC:

AN:

58586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

142568

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69216

African (AFR)

AF:

0.00

AC:

AN:

37062

American (AMR)

AF:

0.00

AC:

AN:

14336

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3376

East Asian (EAS)

AF:

0.00

AC:

AN:

4638

South Asian (SAS)

AF:

0.00

AC:

AN:

4348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9948

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65746

Other (OTH)

AF:

0.00

AC:

AN:

1926

Alfa

AF:

0.00

Hom.:

2377

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.022

(source)

DANN

Benign

0.71

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.015

M_CAP

Benign

0.0044

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

PhyloP100

-1.4

PrimateAI

Benign

0.18

PROVEAN

Benign

-1.9

REVEL

Benign

0.0040

Sift

Benign

0.25

Sift4G

Benign

0.35

Vest4

0.15

MutPred

0.39

Loss of MoRF binding (P = 0.0793)

MVP

0.12

MPC

1.9

ClinPred

0.13

GERP RS

-7.6

PromoterAI

0.0055

Neutral

(source)

gMVP

0.59

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000075

dbscSNV1_RF

Benign

0.044

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over